The NFL never shies away from loading up the opening week with must-see matchups, and the Week 1 NFL schedule is no different. From divisional battles like Cowboys vs. Giants (+2.5) and Chiefs vs. Broncos (+2.5) to Aaron Rodgers’ last ride in Steelers vs. Falcons (+3), you have a bevy of intriguing options to place Week 1 NFL bets on. The slimmest of NFL spreads comes via Texans vs. Bills (-1.5) and Vikings vs. Packers (-1.5), while the largest Week 1 NFL line comes in Chargers vs. Cardinals (+10.5).

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The NFL odds for the opening slate are an estimation more so than any other week as Vegas has no actual competitive game action to go off. In hindsight, some of these Week 1 NFL spreads may end up looking absurd, but that also will make Week 1 NFL predictions all the more difficult. Which lines are way off, and which teams present extreme value with Week 1 NFL picks?

Before locking in any NFL bets, make sure you see what SportsLine’s advanced computer model has to say. 

The model, which simulates every NFL game 10,000 times, is up well over $7,000 for $100 players on top-rated NFL picks since its inception. The model enters the 2026 NFL season on a 53-37 run on top-rated picks dating back to 2024. Anybody following could have seen HUGE returns!

Now, the model has evaluated the latest NFL odds, simulated every snap for Week 1 of the 2025 NFL season, and the results are in.

We can tell you one of the model’s strongest Week 1 NFL picks is that the Jaguars (-7.5, 40.5) cover at home versus Cleveland in a Sunday 1 p.m. ET kickoff.  The model has the Jags prevailing versus the spread well over 50% of the time, with the Over hitting in 60% of simulations. Another one of its Week 1 NFL predictions: the Eagles (-4.5, 47.5) cover versus the Commanders at home on Sunday at 4:25 p.m. ET. Philly is forecasted to cover the spread in nearly 60% of simulations in an A-rated pick.

The model has also made the call on who wins and covers in every other NFL game this week and just revealed multiple underdogs projected to outright win, potentially providing a huge payday! You ABSOLUTELY NEED to see its NFL picks for every game before you make any NFL bets of your own!